A considerable body of prior art exists encompassing compounds of 3-(aryloxy)-2-hydroxypropylamine series which possess beta-adrenergic receptor blocking activity and/or vasodilating properties and are useful in treatment of cardiovascular diseases. Such compounds can be structurally typified by propranolol, chemically, 1-isopropyl-amino-3-(1-naphthoxy)-2-propanol. Propranolol and some related naphthoxypropanolamines are the subject of U.S. Pat. No. 3,337,628 issued Aug. 22, 1967. Numerous subsequent patents have been granted covering carbocyclic ethers in which other aromatic rings or heterocyclic systems replace the naphthoxy group of propranolol. Numerous variations have also been disclosed for the amino substituent of the propanolamine moiety. Reference patents, which are mentioned hereinbelow, generally disclose cardiovascular agents possessing the following generic structure (1): ##STR1## wherein Y is aryl or hetaryl, unsubstituted or substituted; and Z is alkyl, alkylphenyl, or alkylhetaryl.
Matier, et al., in U.S. Pat. No. 4,321,398 issued Mar. 23, 1982, discloses compounds wherein Y is substituted phenyl and Z is an alkylthienyl or alkylbenzothienyl moiety.
Attention is also called to the application Ser. No. 414,748 of Kreighbaum, filed Sept. 3, 1982, which discloses compounds wherein Y is a substituted pyridine system and Z is an alkylindolyl moiety.
Frei, et al., South African Patent Application No. 741070, convention filing data of Feb. 20, 1973, discloses compounds wherein Y is a pyrimidine ring system, either unsubstituted or substituted with a group selected from a long list of possible substituents. Z for this series of compounds can be alkyl or alkylphenyl. No hydrazine or hydrazone substituents on the pyrimidine ring are disclosed in this case.
Jaeggi, et al., U.S. Pat. No. 4,139,623 issued Feb. 13, 1979, also discloses compounds wherein Y is a substituted pyrimidine ring but Z is alkoxyphenyl or alkoxypyrimidine.
Wasson, et al., disclosed subject matter in divisional patents, U.S. Pat. No. 4,042,586 issued Aug. 16, 1977, and U.S. Pat. No. 4,193,995 issued Mar. 18, 1980; relating to compounds in which Z was alkyl, alkylphenyl, or alkylindolyl but Y was a pyrazine ring system.
Similarly, Dorigotti, et al., U.S. Pat. No. 4,324,788 issued Apr. 13, 1982, disclosed compounds wherein Z is alkyl, cycloalkyl, or alkylphenyl but Y is a hydrazone-substituted pyridazine ring system.
These reference patents can be distinguished from the instant invention in view of one or more of the following distinguishing characteristics. Compounds of the instant invention (1) are comprised of a propoxy-pyrimidine ring structural component, (2) the pyrimidine ring is optimally substituted in the 2- position with a hydrazino or hydrazono moiety, and (3) Z can be alkylthienyl, alkylbenzothienyl, alkylbenzofuranyl, or alkylbenzimidazolyl in addition to alkylindolyl, alkylphenyl, and alkyl.